Diffusion kurtosis imaging detects the time‐dependent progress of pathological changes in the oral rotenone mouse model of Parkinson's disease. Issue 3 (5th July 2021)

• Record Type: Journal Article
• Authors: Khairnar, Amit; Ruda‐Kucerova, Jana; Arab, Anas; Hadjistyllis, Constantinos; Sejnoha Minsterova, Alzbeta; Shang, Qi; Chovsepian, Alexandra; Drazanova, Eva; Szabó, Nikoletta; Starcuk, Zenon; Rektorova, Irena; Pan‐Montojo, Francisco
• Is Part Of: Journal of neurochemistry. Volume 158:Issue 3(2021)
• Page Start: 779
• Page End: 797
• Publication Date: 2021-07-05
• Subjects: alpha synuclein -- diffusion kurtosis imaging -- MRI -- Parkinson -- rotenone -- s disease -- tract‐based spatial statistics; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.15449
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Clinical diagnosis of Parkinson's disease (PD) occurs typically when a substantial proportion of dopaminergic neurons in the substantia nigra (SN) already died, and the first motor symptoms appear. Therefore, tools enabling the early diagnosis of PD are essential to identify early‐stage PD patients in which neuroprotective treatments could have a significant impact. Here, we test the utility and sensitivity of the diffusion kurtosis imaging (DKI) in detecting progressive microstructural changes in several brain regions of mice exposed to chronic intragastric administration of rotenone, a mouse model that mimics the spatiotemporal progression of PD‐like pathology from the ENS to the SN as described by Braak's staging. Our results show that DKI, especially kurtosis, can detect the progression of pathology‐associated changes throughout the CNS. Increases in mean kurtosis were first observed in the dorsal motor nucleus of the vagus (DMV) after 2 months of exposure to rotenone and before the loss of dopaminergic neurons in the SN occurred. Remarkably, we also show that limited exposure to rotenone for 2 months is enough to trigger the progression of the disease in the absence of the environmental toxin, thus suggesting that once the first pathological changes in one region appear, they can self‐perpetuate and progress within the CNS. Overall, our results show that DKI can be a useful radiological marker for the early detection and monitoring of PD pathology progression in patients with the potential to improve the clinical diagnosis and the development of neuroprotective treatments. Abstract : Early diagnosis of Parkinson's disease (PD) is a need of an hour due to which neuroprotective treatments could have a significant impact. We tested the utility and sensitivity of the diffusion kurtosis imaging (DKI) in intragastric rotenone model which mimics the spatiotemporal progression of PD‐like pathology from the enteric neurons to the substantia nigra (SN). Mean kurtosis changes were first observed in the dorsal motor nucleus of the vagus before the loss of dopaminergic neurons in the SN and later in nigrostriatal regions suggesting DKI can be a useful radiological marker for the early detection and monitoring of PD pathology.